@article{HommersRichterYangetal.2018,
  author    = {Hommers, L. G. and Richter, J. and Yang, Y. and Raab, A. and Baumann, C. and Lang, K. and Schiele, M. A. and Weber, H. and Wittmann, A. and Wolf, C. and Alpers, G. W. and Arolt, V. and Domschke, K. and Fehm, L. and Fydrich, T. and Gerlach, A. and Gloster, A. T. and Hamm, A. O. and Helbig-Lang, S. and Kircher, T. and Lang, T. and Pan{\´e}-Farr{\´e}, C. A. and Pauli, P. and Pfleiderer, B. and Reif, A. and Romanos, M. and Straube, B. and Str{\"o}hle, A. and Wittchen, H.-U. and Frantz, S. and Ertl, G. and Lohse, M. J. and Lueken, U. and Deckert, J.},
  title     = {A functional genetic variation of SLC6A2 repressor hsa-miR-579-3p upregulates sympathetic noradrenergic processes of fear and anxiety},
  series = {Translational Psychiatry},
  volume    = {8},
  journal   = {Translational Psychiatry},
  doi       = {10.1038/s41398-018-0278-4},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-322497},
  year      = {2018},
  abstract  = {Increased sympathetic noradrenergic signaling is crucially involved in fear and anxiety as defensive states. MicroRNAs regulate dynamic gene expression during synaptic plasticity and genetic variation of microRNAs modulating noradrenaline transporter gene (SLC6A2) expression may thus lead to altered central and peripheral processing of fear and anxiety. In silico prediction of microRNA regulation of SLC6A2 was confirmed by luciferase reporter assays and identified hsa-miR-579-3p as a regulating microRNA. The minor (T)-allele of rs2910931 (MAFcases = 0.431, MAFcontrols = 0.368) upstream of MIR579 was associated with panic disorder in patients (pallelic = 0.004, ncases = 506, ncontrols = 506) and with higher trait anxiety in healthy individuals (pASI = 0.029, pACQ = 0.047, n = 3112). Compared to the major (A)-allele, increased promoter activity was observed in luciferase reporter assays in vitro suggesting more effective MIR579 expression and SLC6A2 repression in vivo (p = 0.041). Healthy individuals carrying at least one (T)-allele showed a brain activation pattern suggesting increased defensive responding and sympathetic noradrenergic activation in midbrain and limbic areas during the extinction of conditioned fear. Panic disorder patients carrying two (T)-alleles showed elevated heart rates in an anxiety-provoking behavioral avoidance test (F(2, 270) = 5.47, p = 0.005). Fine-tuning of noradrenaline homeostasis by a MIR579 genetic variation modulated central and peripheral sympathetic noradrenergic activation during fear processing and anxiety. This study opens new perspectives on the role of microRNAs in the etiopathogenesis of anxiety disorders, particularly their cardiovascular symptoms and comorbidities.},
  language  = {en}
}
@article{CouchWangMcGuffogetal.2013,
  author    = {Couch, Fergus J. and Wang, Xianshu and McGuffog, Lesley and Lee, Andrew and Olswold, Curtis and Kuchenbaecker, Karoline B. and Soucy, Penny and Fredericksen, Zachary and Barrowdale, Daniel and Dennis, Joe and Gaudet, Mia M. and Dicks, Ed and Kosel, Matthew and Healey, Sue and Sinilnikova, Olga M. and Lee, Adam and Bacot, Fran{\c{c}}ios and Vincent, Daniel and Hogervorst, Frans B. L. and Peock, Susan and Stoppa-Lyonnet, Dominique and Jakubowska, Anna and Radice, Paolo and Schmutzler, Rita Katharina and Domchek, Susan M. and Piedmonte, Marion and Singer, Christian F. and Friedman, Eitan and Thomassen, Mads and Hansen, Thomas V. O. and Neuhausen, Susan L. and Szabo, Csilla I. and Blanco, Ingnacio and Greene, Mark H. and Karlan, Beth Y. and Garber, Judy and Phelan, Catherine M. and Weitzel, Jeffrey N. and Montagna, Marco and Olah, Edith and Andrulis, Irene L. and Godwin, Andrew K. and Yannoukakos, Drakoulis and Goldgar, David E. and Caldes, Trinidad and Nevanlinna, Heli and Osorio, Ana and Terry, Mary Beth and Daly, Mary B. and van Rensburg, Elisabeth J. and Hamann, Ute and Ramus, Susan J. and Toland, Amanda Ewart and Caligo, Maria A. and Olopade, Olufunmilayo I. and Tung, Nadine and Claes, Kathleen and Beattie, Mary S. and Southey, Melissa C. and Imyanitov, Evgeny N. and Tischkowitz, Marc and Janavicius, Ramunas and John, Esther M. and Kwong, Ava and Diez, Orland and Kwong, Ava and Balma{\~n}a, Judith and Barkardottir, Rosa B. and Arun, Banu K. and Rennert, Gad and Teo, Soo-Hwang and Ganz, Patricia A. and Campbell, Ian and van der Hout, Annemarie H. and van Deurzen, Carolien H. M. and Seynaeve, Caroline and Garcia, Encarna B. G{\´o}mez and van Leeuwen, Flora E. and Meijers-Heijboer, Hanne E. J. and Gille, Johannes J. P. and Ausems, Magreet G. E. M. and Blok, Marinus J. and Ligtenberg, Marjolinjin J. L. and Rookus, Matti A. and Devilee, Peter and Verhoef, Senno and van Os, Theo A. M. and Wijnen, Juul T. and Frost, Debra and Ellis, Steve and Fineberg, Elena and Platte, Radke and Evans, D. Gareth and Izatt, Luise and Eeles, Rosalind A. and Adlard, Julian and Eccles, Diana M. and Cook, Jackie and Brewer, Carole and Douglas, Fiona and Hodgson, Shirley and Morrison, Patrick J. and Side, Lucy E. and Donaldson, Alan and Houghton, Catherine and Rogers, Mark T. and Dorkins, Huw and Eason, Jacqueline and Gregory, Helen and McCann, Emma and Murray, Alex and Calender, Alain and Hardouin, Agn{\`e}s and Berthet, Pascaline and Delnatte, Capucine and Nogues, Catherine and Lasset, Christine and Houdayer, Claude and Leroux,, Dominique and Rouleau, Etienne and Prieur, Fabienne and Damiola, Francesca and Sobol, Hagay and Coupier, Isabelle and Venat-Bouvet, Laurence and Castera, Laurent and Gauthier-Villars, Marion and L{\´e}on{\´e}, M{\´e}lanie and Pujol, Pascal and Mazoyer, Sylvie and Bignon, Yves-Jean and Zlowocka-Perlowska, Elzbieta and Gronwald, Jacek and Lubinski,, Jan and Durda, Katarzyna and Jaworska, Katarzyna and Huzarski, Tomasz and Spurdle, Amanda B. and Viel, Alessandra and Peissel, Bernhard and Bonanni, Bernardo and Melloni, Guilia and Ottini, Laura and Papi, Laura and Varesco, Liliana and Tibiletti, Maria Grazia and Peterlongo, Paolo and Volorio, Sara and Manoukian, Siranoush and Pensotti, Valeria and Arnold, Norbert and Engel, Christoph and Deissler, Helmut and Gadzicki, Dorothea and Gehrig, Andrea and Kast, Karin and Rhiem, Kerstin and Meindl, Alfons and Niederacher, Dieter and Ditsch, Nina and Plendl, Hansjoerg and Preisler-Adams, Sabine and Engert, Stefanie and Sutter, Christian and Varon-Mateeva, Raymenda and Wappenschmidt, Barbara and Weber, Bernhard H. F. and Arver, Brita and Stenmark-Askmalm, Marie and Loman, Niklas and Rosenquist, Richard and Einbeigi, Zakaria and Nathanson, Katherine L. and Rebbeck, Timothy R. and Blank, Stephanie V. and Cohn, David E. and Rodriguez, Gustavo C. and Small, Laurie and Friedlander, Michael and Bae-Jump, Victoria L. and Fink-Retter, Anneliese and Rappaport, Christine and Gschwantler-Kaulich, Daphne and Pfeiler, Georg and Tea, Muy-Kheng and Lindor, Noralane M. and Kaufman, Bella and Paluch, Shani Shimon and Laitman, Yael and Skytte, Anne-Bine and Gerdes, Anne-Marie and Pedersen, Inge Sokilde and Moeller, Sanne Traasdahl and Kruse, Torben A. and Jensen, Uffe Birk and Vijai, Joseph and Sarrel, Kara and Robson, Mark and Kauff, Noah and Mulligan, Anna Marie and Glendon, Gord and Ozcelik, Hilmi and Ejlertsen, Bent and Nielsen, Finn C. and J{\o}nson, Lars and Andersen, Mette K. and Ding, Yuan Chun and Steele, Linda and Foretova, Lenka and Teul{\´e}, Alex and Lazaro, Conxi and Brunet, Joan and Pujana, Miquel Angel and Mai, Phuong L. and Loud, Jennifer T. and Walsh, Christine and Lester, Jenny and Orsulic, Sandra and Narod, Steven A. and Herzog, Josef and Sand, Sharon R. and Tognazzo, Silvia and Agata, Simona and Vaszko, Tibor and Weaver, Joellen and Stravropoulou, Alexandra V. and Buys, Saundra S. and Romero, Atocha and de la Hoya, Miguel and Aittom{\"a}ki, Kristiina and Muranen, Taru A. and Duran, Mercedes and Chung, Wendy K. and Lasa, Adriana and Dorfling, Cecilia M. and Miron, Alexander and Benitez, Javier and Senter, Leigha and Huo, Dezheng and Chan, Salina B. and Sokolenko, Anna P. and Chiquette, Jocelyne and Tihomirova, Laima and Friebel, Tara M. and Agnarsson, Bjarne A. and Lu, Karen H. and Lejbkowicz, Flavio and James, Paul A. and Hall, Per and Dunning, Alison M. and Tessier, Daniel and Cunningham, Julie and Slager, Susan L. and Chen, Wang and Hart, Steven and Stevens, Kristen and Simard, Jacques and Pastinen, Tomi and Pankratz, Vernon S. and Offit, Kenneth and Easton, Douglas F. and Chenevix-Trench, Georgia and Antoniou, Antonis C.},
  title     = {Genome-Wide Association Study in BRCA1 Mutation Carriers Identifies Novel Loci Associated with Breast and Ovarian Cancer Risk},
  series = {PLOS Genetics},
  volume    = {9},
  journal   = {PLOS Genetics},
  number    = {3},
  issn      = {1553-7404},
  doi       = {10.1371/journal.pgen.1003212},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-127947},
  pages     = {e1003212},
  year      = {2013},
  abstract  = {BRCA1-associated breast and ovarian cancer risks can be modified by common genetic variants. To identify further cancer risk-modifying loci, we performed a multi-stage GWAS of 11,705 BRCA1 carriers (of whom 5,920 were diagnosed with breast and 1,839 were diagnosed with ovarian cancer), with a further replication in an additional sample of 2,646 BRCA1 carriers. We identified a novel breast cancer risk modifier locus at 1q32 for BRCA1 carriers (rs2290854, P = 2.7 x 10(-8), HR = 1.14, 95\% CI: 1.09-1.20). In addition, we identified two novel ovarian cancer risk modifier loci: 17q21.31 (rs17631303, P = 1.4 x 10(-8), HR = 1.27, 95\% CI: 1.17-1.38) and 4q32.3 (rs4691139, P = 3.4 x 10(-8), HR = 1.20, 95\% CI: 1.17-1.38). The 4q32.3 locus was not associated with ovarian cancer risk in the general population or BRCA2 carriers, suggesting a BRCA1-specific association. The 17q21.31 locus was also associated with ovarian cancer risk in 8,211 BRCA2 carriers (P = 2 x 10(-4)). These loci may lead to an improved understanding of the etiology of breast and ovarian tumors in BRCA1 carriers. Based on the joint distribution of the known BRCA1 breast cancer risk-modifying loci, we estimated that the breast cancer lifetime risks for the 5\% of BRCA1 carriers at lowest risk are 28\%-50\% compared to 81\%-100\% for the 5\% at highest risk. Similarly, based on the known ovarian cancer risk-modifying loci, the 5\% of BRCA1 carriers at lowest risk have an estimated lifetime risk of developing ovarian cancer of 28\% or lower, whereas the 5\% at highest risk will have a risk of 63\% or higher. Such differences in risk may have important implications for risk prediction and clinical management for BRCA1 carriers.},
  language  = {en}
}
@article{StraubeReifRichteretal.2014,
  author    = {Straube, B. and Reif, A. and Richter, J. and Lueken, U. and Weber, H. and Arolt, V. and Jansen, A. and Zwanzger, P. and Domschke, K. and Pauli, P. and Konrad, C. and Gerlach, A. L. and Lang, T. and Fydrich, T. and Alpers, G. W. and Stroehle, A. and Wittmann, A. and Pfleiderer, B. and Wittchen, H.-U. and Hamm, A. and Deckert, J. and Kircher, T.},
  title     = {The functional - 1019C/G HTR1A polymorphism and mechanisms of fear},
  series = {Translational Psychiatry},
  volume    = {4},
  journal   = {Translational Psychiatry},
  issn      = {2158-3188},
  doi       = {10.1038/tp.2014.130},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-114369},
  pages     = {e490},
  year      = {2014},
  abstract  = {Serotonin receptor 1A gene (HTR1A) knockout mice show pronounced defensive behaviour and increased fear conditioning to ambiguous conditioned stimuli. Such behaviour is a hallmark of pathological human anxiety, as observed in panic disorder with agoraphobia (PD/AG). Thus, variations in HTR1A might contribute to neurophysiological differences within subgroups of PD/AG patients. Here, we tested this hypothesis by combining genetic with behavioural techniques and neuroimaging. In a clinical multicentre trial, patients with PD/AG received 12 sessions of manualized cognitive-behavioural therapy (CBT) and were genotyped for HTR1A rs6295. In four subsamples of this multicentre trial, exposure behaviour (n = 185), defensive reactivity measured using a behavioural avoidance test (BAT; before CBT: n = 245; after CBT: n = 171) and functional magnetic resonance imaging (fMRI) data during fear conditioning were acquired before and after CBT (n = 39). HTR1A risk genotype (GG) carriers more often escaped during the BAT before treatment. Exploratory fMRI results suggest increased activation of the amygdala in response to threat as well as safety cues before and after treatment in GG carriers. Furthermore, GG carriers demonstrated reduced effects of CBT on differential conditioning in regions including the bilateral insulae and the anterior cingulate cortex. Finally, risk genotype carriers demonstrated reduced self-initiated exposure behaviour to aversive situations. This study demonstrates the effect of HTR1A variation on defensive behaviour, amygdala activity, CBT-induced neural plasticity and normalization of defence behaviour in PD/AG. Our results, therefore, translate evidence from animal studies to humans and suggest a central role for HTR1A in differentiating subgroups of patients with anxiety disorders.},
  language  = {en}
}
@article{AboagyeWeberMerdianetal.2021,
  author    = {Aboagye, B. and Weber, T. and Merdian, H. L. and Bartsch, D. and Lesch, K. P. and Waider, J.},
  title     = {Serotonin deficiency induced after brain maturation rescues consequences of early life adversity},
  series = {Scientific Reports},
  volume    = {11},
  journal   = {Scientific Reports},
  number    = {1},
  issn      = {2045-2322},
  doi       = {10.1038/s41598-021-83592-4},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-258626},
  year      = {2021},
  abstract  = {Brain serotonin (5-HT) system dysfunction is implicated in depressive disorders and acute depletion of 5-HT precursor tryptophan has frequently been used to model the influence of 5-HT deficiency on emotion regulation. Tamoxifen (TAM)-induced Cre/loxP-mediated inactivation of the tryptophan hydroxylase-2 gene (Tph2) was used to investigate the effects of provoked 5-HT deficiency in adult mice (Tph2 icKO) previously subjected to maternal separation (MS). The efficiency of Tph2 inactivation was validated by immunohistochemistry and HPLC. The impact of Tph2 icKO in interaction with MS stress (Tph2 icKOxMS) on physiological parameters, emotional behavior and expression of 5-HT system-related marker genes were assessed. Tph2 icKO mice displayed a significant reduction in 5-HT immunoreactive cells and 5-HT concentrations in the rostral raphe region within four weeks following TAM treatment. Tph2 icKO and MS differentially affected food and water intake, locomotor activity as well as panic-like escape behavior. Tph2 icKO prevented the adverse effects of MS stress and altered the expression of the genes previously linked to stress and emotionality. In conclusion, an experimental model was established to study the behavioral and neurobiological consequences of 5-HT deficiency in adulthood in interaction with early-life adversity potentially affecting brain development and the pathogenesis of depressive disorders.},
  language  = {en}
}
@article{BarlinnWinzerWorthmannetal.2021,
  author    = {Barlinn, J. and Winzer, S. and Worthmann, H. and Urbanek, C. and H{\"a}usler, K. G. and G{\"u}nther, A. and Erdur, H. and G{\"o}rtler, M. and Busetto, L. and Wojciechowski, C. and Schmitt, J. and Shah, Y. and B{\"u}chele, B. and Sokolowski, P. and Kraya, T. and Merkelbach, S. and Rosengarten, B. and Stangenberg-Gliss, K. and Weber, J. and Schlachetzki, F. and Abu-Mugheisib, M. and Petersen, M. and Schwartz, A. and Palm, F. and Jowaed, A. and Volbers, B. and Zickler, P. and Remi, J. and Bardutzky, J. and B{\"o}sel, J. and Audebert, H. J. and Hubert, G. J. and Gumbinger, C.},
  title     = {Telemedizin in der Schlaganfallversorgung - versorgungsrelevant f{\"u}r Deutschland},
  series = {Der Nervenarzt},
  volume    = {92},
  journal   = {Der Nervenarzt},
  number    = {6},
  issn      = {0028-2804},
  doi       = {10.1007/s00115-021-01137-6},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-307752},
  pages     = {593-601},
  year      = {2021},
  abstract  = {Hintergrund und Ziel Telemedizinische Schlaganfall-Netzwerke tragen dazu bei, die Schlaganfallversorgung und insbesondere den Zugang zu zeitkritischen Schlaganfalltherapien in vorrangig strukturschwachen, l{\"a}ndlichen Regionen zu gew{\"a}hrleisten. Ziel ist eine Darstellung der Nutzungsfrequenz und regionalen Verteilung dieser Versorgungsstruktur. Methoden Die Kommission „Telemedizinische Schlaganfallversorgung" der Deutschen Schlaganfall-Gesellschaft f{\"u}hrte eine Umfragestudie in allen Schlaganfall-Netzwerken durch. Ergebnisse In Deutschland sind 22 telemedizinische Schlaganfall-Netzwerke aktiv, welche insgesamt 43 Zentren (pro Netzwerk: Median 1,5, Interquartilsabstand [IQA] 1-3) sowie 225 Kooperationskliniken (pro Netzwerk: Median 9, IQA 4-17) umfassen und an einem unmittelbaren Zugang zur Schlaganfallversorgung f{\"u}r 48 Mio. Menschen teilhaben. Im Jahr 2018 wurden 38.211 Telekonsile (pro Netzwerk: Median 1340, IQA 319-2758) durchgef{\"u}hrt. Die Thrombolyserate betrug 14,1 \% (95 \%-Konfidenzintervall 13,6-14,7 \%), eine Verlegung zur Thrombektomie wurde bei 7,9 \% (95 \%-Konfidenzintervall 7,5-8,4 \%) der isch{\"a}mischen Schlaganfallpatienten initiiert. Das Finanzierungssystem ist uneinheitlich mit einem Verg{\"u}tungssystem f{\"u}r die Zentrumsleistungen in nur drei Bundesl{\"a}ndern. Diskussion Etwa jeder 10. Schlaganfallpatient wird telemedizinisch behandelt. Die telemedizinischen Schlaganfall-Netzwerke erreichen vergleichbar hohe Lyseraten und Verlegungen zur Thrombektomie wie neurologische Stroke-Units und tragen zur Sicherstellung einer fl{\"a}chendeckenden Schlaganfallversorgung bei. Eine netzwerk{\"u}bergreifende Sicherstellung der Finanzierung und einheitliche Erhebung von Qualit{\"a}tssicherungsdaten haben das Potenzial diese Versorgungsstruktur zuk{\"u}nftig weiter zu st{\"a}rken.},
  language  = {de}
}
@article{SimsekyilmazLiehnWeinandyetal.2016,
  author    = {Simsekyilmaz, Sakine and Liehn, Elisa A. and Weinandy, Stefan and Schreiber, Fabian and Megens, Remco T. A. and Theelen, Wendy and Smeets, Ralf and Jockenh{\"o}vel, Stefan and Gries, Thomas and M{\"o}ller, Martin and Klee, Doris and Weber, Christian and Zernecke, Alma},
  title     = {Targeting In-Stent-Stenosis with RGD- and CXCL1-Coated Mini-Stents in Mice},
  series = {PLoS ONE},
  volume    = {11},
  journal   = {PLoS ONE},
  number    = {5},
  doi       = {10.1371/journal.pone.0155829},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-179745},
  year      = {2016},
  abstract  = {Atherosclerotic lesions that critically narrow the artery can necessitate an angioplasty and stent implantation. Long-term therapeutic effects, however, are limited by excessive arterial remodeling. We here employed a miniaturized nitinol-stent coated with star-shaped polyethylenglycole (star-PEG), and evaluated its bio-functionalization with RGD and CXCL1 for improving in-stent stenosis after implantation into carotid arteries of mice. Nitinol foils or stents (bare metal) were coated with star-PEG, and bio-functionalized with RGD, or RGD/CXCL1. Cell adhesion to star-PEG-coated nitinol foils was unaltered or reduced, whereas bio-functionalization with RGD but foremost RGD/CXCL1 increased adhesion of early angiogenic outgrowth cells (EOCs) and endothelial cells but not smooth muscle cells when compared with bare metal foils. Stimulation of cells with RGD/CXCL1 furthermore increased the proliferation of EOCs. In vivo, bio-functionalization with RGD/CXCL1 significantly reduced neointima formation and thrombus formation, and increased re-endothelialization in apoE\(^{-/-}\) carotid arteries compared with bare-metal nitinol stents, star-PEG-coated stents, and stents bio-functionalized with RGD only. Bio-functionalization of star-PEG-coated nitinol-stents with RGD/CXCL1 reduced in-stent neointima formation. By supporting the adhesion and proliferation of endothelial progenitor cells, RGD/CXCL1 coating of stents may help to accelerate endothelial repair after stent implantation, and thus may harbor the potential to limit the complication of in-stent restenosis in clinical approaches.},
  language  = {en}
}
@article{GroebnerWorstWeischenfeldtetal.2018,
  author    = {Gr{\"o}bner, Susanne N. and Worst, Barbara C. and Weischenfeldt, Joachim and Buchhalter, Ivo and Kleinheinz, Kortine and Rudneva, Vasilisa A. and Johann, Pascal D. and Balasubramanian, Gnana Prakash and Segura-Wang, Maia and Brabetz, Sebastian and Bender, Sebastian and Hutter, Barbara and Sturm, Dominik and Pfaff, Elke and H{\"u}bschmann, Daniel and Zipprich, Gideon and Heinold, Michael and Eils, J{\"u}rgen and Lawerenz, Christian and Erkek, Serap and Lambo, Sander and Waszak, Sebastian and Blattmann, Claudia and Borkhardt, Arndt and Kuhlen, Michaela and Eggert, Angelika and Fulda, Simone and Gessler, Manfred and Wegert, Jenny and Kappler, Roland and Baumhoer, Daniel and Stefan, Burdach and Kirschner-Schwabe, Renate and Kontny, Udo and Kulozik, Andreas E. and Lohmann, Dietmar and Hettmer, Simone and Eckert, Cornelia and Bielack, Stefan and Nathrath, Michaela and Niemeyer, Charlotte and Richter, G{\"u}nther H. and Schulte, Johannes and Siebert, Reiner and Westermann, Frank and Molenaar, Jan J. and Vassal, Gilles and Witt, Hendrik and Burkhardt, Birgit and Kratz, Christian P. and Witt, Olaf and van Tilburg, Cornelis M. and Kramm, Christof M. and Fleischhack, Gudrun and Dirksen, Uta and Rutkowski, Stefan and Fr{\"u}hwald, Michael and Hoff, Katja von and Wolf, Stephan and Klingebeil, Thomas and Koscielniak, Ewa and Landgraf, Pablo and Koster, Jan and Resnick, Adam C. and Zhang, Jinghui and Liu, Yanling and Zhou, Xin and Waanders, Angela J. and Zwijnenburg, Danny A. and Raman, Pichai and Brors, Benedikt and Weber, Ursula D. and Northcott, Paul A. and Pajtler, Kristian W. and Kool, Marcel and Piro, Rosario M. and Korbel, Jan O. and Schlesner, Matthias and Eils, Roland and Jones, David T. W. and Lichter, Peter and Chavez, Lukas and Zapatka, Marc and Pfister, Stefan M.},
  title     = {The landscape of genomic alterations across childhood cancers},
  series = {Nature},
  volume    = {555},
  journal   = {Nature},
  organization    = {ICGC PedBrain-Seq Project, ICGC MMML-Seq Project,},
  doi       = {10.1038/nature25480},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-229579},
  pages     = {321-327},
  year      = {2018},
  abstract  = {Pan-cancer analyses that examine commonalities and differences among various cancer types have emerged as a powerful way to obtain novel insights into cancer biology. Here we present a comprehensive analysis of genetic alterations in a pan-cancer cohort including 961 tumours from children, adolescents, and young adults, comprising 24 distinct molecular types of cancer. Using a standardized workflow, we identified marked differences in terms of mutation frequency and significantly mutated genes in comparison to previously analysed adult cancers. Genetic alterations in 149 putative cancer driver genes separate the tumours into two classes: small mutation and structural/copy-number variant (correlating with germline variants). Structural variants, hyperdiploidy, and chromothripsis are linked to TP53 mutation status and mutational signatures. Our data suggest that 7-8\% of the children in this cohort carry an unambiguous predisposing germline variant and that nearly 50\% of paediatric neoplasms harbour a potentially druggable event, which is highly relevant for the design of future clinical trials.},
  language  = {en}
}
@article{GottschalkRichterZiegleretal.2019,
  author    = {Gottschalk, Michael G. and Richter, Jan and Ziegler, Christiane and Schiele, Miriam A. and Mann, Julia and Geiger, Maximilian J. and Schartner, Christoph and Homola, Gy{\"o}rgy A. and Alpers, Georg W. and B{\"u}chel, Christian and Fehm, Lydia and Fydrich, Thomas and Gerlach, Alexander L. and Gloster, Andrew T. and Helbig-Lang, Sylvia and Kalisch, Raffael and Kircher, Tilo and Lang, Thomas and Lonsdorf, Tina B. and Pan{\´e}-Farr{\´e}, Christiane A. and Str{\"o}hle, Andreas and Weber, Heike and Zwanzger, Peter and Arolt, Volker and Romanos, Marcel and Wittchen, Hans-Ulrich and Hamm, Alfons and Pauli, Paul and Reif, Andreas and Deckert, J{\"u}rgen and Neufang, Susanne and H{\"o}fler, Michael and Domschke, Katharina},
  title     = {Orexin in the anxiety spectrum: association of a HCRTR1 polymorphism with panic disorder/agoraphobia, CBT treatment response and fear-related intermediate phenotypes},
  series = {Translational Psychiatry},
  volume    = {9},
  journal   = {Translational Psychiatry},
  doi       = {10.1038/s41398-019-0415-8},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-227479},
  year      = {2019},
  abstract  = {Preclinical studies point to a pivotal role of the orexin 1 (OX1) receptor in arousal and fear learning and therefore suggest the HCRTR1 gene as a prime candidate in panic disorder (PD) with/without agoraphobia (AG), PD/AG treatment response, and PD/AG-related intermediate phenotypes. Here, a multilevel approach was applied to test the non-synonymous HCRTR1 C/T Ile408Val gene variant (rs2271933) for association with PD/AG in two independent case-control samples (total n = 613 cases, 1839 healthy subjects), as an outcome predictor of a six-weeks exposure-based cognitive behavioral therapy (CBT) in PD/AG patients (n = 189), as well as with respect to agoraphobic cognitions (ACQ) (n = 483 patients, n = 2382 healthy subjects), fMRI alerting network activation in healthy subjects (n = 94), and a behavioral avoidance task in PD/AG pre- and post-CBT (n = 271). The HCRTR1 rs2271933 T allele was associated with PD/AG in both samples independently, and in their meta-analysis (p = 4.2 × 10-7), particularly in the female subsample (p = 9.8 × 10-9). T allele carriers displayed a significantly poorer CBT outcome (e.g., Hamilton anxiety rating scale: p = 7.5 × 10-4). The T allele count was linked to higher ACQ sores in PD/AG and healthy subjects, decreased inferior frontal gyrus and increased locus coeruleus activation in the alerting network. Finally, the T allele count was associated with increased pre-CBT exposure avoidance and autonomic arousal as well as decreased post-CBT improvement. In sum, the present results provide converging evidence for an involvement of HCRTR1 gene variation in the etiology of PD/AG and PD/AG-related traits as well as treatment response to CBT, supporting future therapeutic approaches targeting the orexin-related arousal system.},
  language  = {en}
}
@article{JoosSaadatmandSchnabeletal.2018,
  author    = {Joos, J. P. and Saadatmand, A. R. and Schnabel, C. and Viktorinov{\´a}, I. and Brand, T. and Kramer, M. and Nattel, S. and Dobrev, D. and Tomancak, P. and Backs, J. and Kleinbongard, P. and Heusch, G. and Lorenz, K. and Koch, E. and Weber, S. and El-Armouche, A.},
  title     = {Ectopic expression of S28A-mutated Histone H3 modulates longevity, stress resistance and cardiac function in Drosophila},
  series = {Scientific Reports},
  volume    = {8},
  journal   = {Scientific Reports},
  doi       = {10.1038/s41598-018-21372-3},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-323637},
  year      = {2018},
  abstract  = {Histone H3 serine 28 (H3S28) phosphorylation and de-repression of polycomb repressive complex (PRC)-mediated gene regulation is linked to stress conditions in mitotic and post-mitotic cells. To better understand the role of H3S28 phosphorylation in vivo, we studied a Drosophila strain with ectopic expression of constitutively-activated H3S28A, which prevents PRC2 binding at H3S28, thus mimicking H3S28 phosphorylation. H3S28A mutants showed prolonged life span and improved resistance against starvation and paraquat-induced oxidative stress. Morphological and functional analysis of heart tubes revealed smaller luminal areas and thicker walls accompanied by moderately improved cardiac function after acute stress induction. Whole-exome deep gene-sequencing from isolated heart tubes revealed phenotype-corresponding changes in longevity-promoting and myotropic genes. We also found changes in genes controlling mitochondrial biogenesis and respiration. Analysis of mitochondrial respiration from whole flies revealed improved efficacy of ATP production with reduced electron transport-chain activity. Finally, we analyzed posttranslational modification of H3S28 in an experimental heart failure model and observed increased H3S28 phosphorylation levels in HF hearts. Our data establish a critical role of H3S28 phosphorylation in vivo for life span, stress resistance, cardiac and mitochondrial function in Drosophila. These findings may pave the way for H3S28 phosphorylation as a putative target to treat stress-related disorders such as heart failure.},
  language  = {en}
}
@article{LuekenKuhnYangetal.2017,
  author    = {Lueken, U and Kuhn, M and Yang, Y and Straube, B and Kircher, T and Wittchen, H-U and Pfleiderer, B and Arolt, V and Wittmann, A and Str{\"o}hle, A and Weber, H and Reif, A and Domschke, K and Deckert, J and Lonsdorf, TB},
  title     = {Modulation of defensive reactivity by GLRB allelic variation: converging evidence from an intermediate phenotype approach},
  series = {Translational Psychiatry},
  volume    = {7},
  journal   = {Translational Psychiatry},
  number    = {e1227},
  doi       = {10.1038/tp.2017.186},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-182381},
  year      = {2017},
  abstract  = {Representing a phylogenetically old and very basic mechanism of inhibitory neurotransmission, glycine receptors have been implicated in the modulation of behavioral components underlying defensive responding toward threat. As one of the first findings being confirmed by genome-wide association studies for the phenotype of panic disorder and agoraphobia, allelic variation in a gene coding for the glycine receptor beta subunit (GLRB) has recently been associated with increased neural fear network activation and enhanced acoustic startle reflexes. On the basis of two independent healthy control samples, we here aimed to further explore the functional significance of the GLRB genotype (rs7688285) by employing an intermediate phenotype approach. We focused on the phenotype of defensive system reactivity across the levels of brain function, structure, and physiology. Converging evidence across both samples was found for increased neurofunctional activation in the (anterior) insular cortex in GLRB risk allele carriers and altered fear conditioning as a function of genotype. The robustness of GLRB effects is demonstrated by consistent findings across different experimental fear conditioning paradigms and recording sites. Altogether, findings provide translational evidence for glycine neurotransmission as a modulator of the brain's evolutionary old dynamic defensive system and provide further support for a strong, biologically plausible candidate intermediate phenotype of defensive reactivity. As such, glycine-dependent neurotransmission may open up new avenues for mechanistic research on the etiopathogenesis of fear and anxiety disorders.},
  language  = {en}
}